1. Field of the Invention
This invention relates to 2',3'-dideoxy-4'-thioribonucleosides and to their use as antiviral, especially anti-AIDS agents. This invention is further directed to the intermediates for producing 2',3'-dideoxy-4'-thioribonucleosides.
2. Description of the Related Art
2',3'-Dideoxynucleosides are known to be potent and selective agents for the treatment of AIDS. Within this series of compounds, dideoxycytidine, dideoxyinosine and AZT (3'-azido-3'-deoxythymidine) have been found to be particularly potent. However, each of these compounds produce undesirable side effects.
Thionucleoside analogues of 2',3'-dideoxynucleosides and their use as antiviral agents have not been previously reported.
Several 4'-thionucleosides have been reported in the literature. Reist, et al, J. Am. Chem. Soc., 86, 5658 (1964) disclose L and D forms of 4'-thioriboadenosine. Biological effects of 4'-thioriboadenosine are described in Miura, et al in Purine and Pyrimidin Metabolism in Man, V, Part B, (Plenum Publishing Corp., 1986] p. 667. Richie, et al, Can. J. Chem., 56, 794 (1977) disclose the synthesis of 9-(3-deoxy-4-thio-.beta.-D-erythro-pentofuranosyl)adenine (4'-thiocordycepin). Reist, et al, J. Org. Chem., 33, 189 (1968) describe the synthesis of adenine nucleosides of 4-thio-D-xylose and 4-thio-D-arabinose. Ototani, et al. J. Med. Chem., 17, 535 (1974) disclose the preparation and antitumor activity of 4'-thio-1-.beta.-D-arabinofuranosylcytosine and 2,2'-anhydro-4'-thio-]-.beta.-D-arabinofuranosylcytosine hydrochloride.
Fu, et al, J. Org. Chem., 41, 3831 (1976) disclose a method for the preparation of anomeric methyl-2-deoxy-4-thio-D-erythro-pentofuranosides and suggest that the furanosides could be used as precursors for the synthesis of 2'-deoxy-4'-thionucleosides.